In this Project, we propose to continue the investigation of potentially modifiable nutritional and hormonal risk factors for incident ovarian cancer. This work will use prospectively collected questionnaire data, biological samples, and paraffin-embedded ovarian tumor tissue from women in the Nurses'Health Study (NHS) and NHSII. Although several hypotheses regarding ovarian cancer etiology have been proffered, few modifiable lifestyle risk factors have been identified. We will examine the possible preventive role of vitamin D in ovarian cancer, with the goal of identifying subpopulations who could most benefit from intervention. We also will evaluate three dietary factors: flavonoids, which may reduce risk;lactose in adolescence and adulthood;and acrylamide intake and red blood cell adduct levels, both of which may increase risk. We also will evaluate the role of melatonin and shift work in ovarian carcinogenesis. In addition, we propose to measure circulating markers of inflammation (CPR, IL-6, and TNFa-R2) and tumor markers associated with inflammation (e.g., STATs). We also propose for the first time to focus specifically on fatal ovarian cancer, with an effort to identify risk factors that may predispose women to either having fast-growing tumors or a peritoneal environment susceptible to metastasis. In this same vein, we plan to evaluate hormone receptors in ovarian tumors and their relation to risk factors, with an emphasis on exploring a new model of ovarian carcinogenesis (slow-growing tumors vs. fast-growing tumors) as a way to classify tumors in epidemiologic studies. The Project shares common biological themes with Projects 1 and 2, including the role of vitamin D, melatonin, and the inflammation pathway and interacts closely with Project 4 for methodologic issues. It also shares with the other Projects a strong administrative and scientific infrastructure provided by Cores A (cohort follow-up and data base maintenance), B (confirmation of cancer and cause of death), C (management of the biospecimens) and D (leadership and data analysis). The findings should enhance understanding of the etiology and progression of ovarian cancer and provide guidance for women and their health care providers in their efforts to reduce suffering and death from this disease.
It is difficult to diagnose ovarian cancer, so improving prevention is key for reducing morbidity and mortality. This proposal examines potential preventive agents (vitamin D, melatonin, flavonoids) and risk factors (shiftwork, lactose, acrylamide). Another emphasis is on ovarian etiology (inflammation, hormones), which could lead to better diagnostic and treatment tools, and a focus on risk factors for fatal ovarian cancer.
|Sparks, Jeffrey A; Chen, Chia-Yen; Jiang, Xia et al. (2015) Improved performance of epidemiologic and genetic risk models for rheumatoid arthritis serologic phenotypes using family history. Ann Rheum Dis 74:1522-9|
|Ananthakrishnan, Ashwin N; Du, Mengmeng; Berndt, Sonja I et al. (2015) Red meat intake, NAT2, and risk of colorectal cancer: a pooled analysis of 11 studies. Cancer Epidemiol Biomarkers Prev 24:198-205|
|Tworoger, Shelley S; Rice, Megan S; Rosner, Bernard A et al. (2015) Bioactive prolactin levels and risk of breast cancer: a nested case-control study. Cancer Epidemiol Biomarkers Prev 24:73-80|
|Song, Mingyang; Gong, Jian; Giovannucci, Edward L et al. (2015) Genetic variants of adiponectin and risk of colorectal cancer. Int J Cancer 137:154-64|
|Merola, Joseph F; Wu, Shaowei; Han, Jiali et al. (2015) Psoriasis, psoriatic arthritis and risk of gout in US men and women. Ann Rheum Dis 74:1495-500|
|Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko et al. (2015) Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. Ann Surg Oncol 22:1226-35|
|Bertrand, Kimberly A; Rosner, Bernard; Eliassen, A Heather et al. (2015) Premenopausal plasma 25-hydroxyvitamin D, mammographic density, and risk of breast cancer. Breast Cancer Res Treat 149:479-87|
|Zhou, Jiachen; Kelsey, Karl T; Giovannucci, Edward et al. (2014) Fluid intake and risk of bladder cancer in the Nurses' Health Studies. Int J Cancer 135:1229-37|
|Li, Shanshan; Flint, Alan; Pai, Jennifer K et al. (2014) Dietary fiber intake and mortality among survivors of myocardial infarction: prospective cohort study. BMJ 348:g2659|
|Sun, Qi; Jiménez, Monik C; Townsend, Mary K et al. (2014) Plasma levels of fetuin-A and risk of coronary heart disease in US women: the Nurses' Health Study. J Am Heart Assoc 3:e000939|
Showing the most recent 10 out of 1102 publications